# Paediatric Langerhans Cell Histiocytosis: A 20-Year Single-Centre Retrospective Study of 35 Cases

## TL;DR

This study reviews 35 pediatric cases of Langerhans cell histiocytosis over 20 years, focusing on skeletal lesions, treatment approaches, and outcomes.

## Contribution

A detailed retrospective analysis of pediatric LCH cases with emphasis on skeletal manifestations and treatment outcomes in a single center.

## Key findings

- Skeletal involvement was present in 85.7% of patients, most commonly in the skull.
- Most patients with unifocal disease had excellent outcomes with conservative or systemic therapy.
- Eight patients experienced disease relapse, primarily at skeletal sites.

## Abstract

Background

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of bone marrow-derived histiocytes that most often affects children. Skeletal involvement is the most frequent manifestation of paediatric LCH, but the lesions can mimic malignancy or infection, posing a diagnostic challenge. We present a retrospective case series of 35 paediatric patients with LCH, highlighting skeletal lesion patterns, multisystem involvement, treatment approaches, and clinical outcomes.

Methodology

Medical records and imaging of 35 paediatric patients diagnosed with LCH between 2005 and 2025 in Wales were retrospectively reviewed. Clinical data, including age, sex, site of disease, radiological characteristics, immunohistochemical markers, treatment regimens, and outcomes, were collected and analysed. Disease was classified as unifocal, multifocal, or multisystem. Diagnosis was based on clinical, radiological, and histological findings. Histopathological confirmation was obtained where available, using CD1a, S100, CD68, and Langerin in selected cases. In patients without a biopsy, diagnosis was based on characteristic clinical and radiological features.

Results

The cohort had a median age of four years (range: 19 days to 16 years), with 22 males (62.9%) and 13 females (37.1%). Skeletal involvement occurred in 30 (85.7%) of 35 patients, most commonly affecting the skull (22 cases, 62.9%), followed by the femur, scapula, spine, pelvis, sternum, clavicle, rib, humerus, ulna, and tibia. All lesions were purely lytic, with most appearing ill-defined; two lesions were well-circumscribed. Extra-skeletal involvement occurred in eight patients, affecting the pituitary, skin, lymph nodes, liver, spleen, lungs, and bone marrow. Immunohistochemistry was performed in 28 cases, with most showing positivity for CD1a, S100, and CD68. Ten patients were diagnosed clinically without histology. Genetic testing identified BRAF mutations in four of seven tested patients.

Management was based on disease extent. Nineteen patients with unifocal disease were managed conservatively with observation, biopsy, or curettage. All patients with multifocal or multisystem disease received systemic chemotherapy. Patients treated after 2021 received the LCH-IV protocol, and those treated before 2017 received LCH-III. All 35 patients were alive at the last follow-up. Eight experienced disease relapse, primarily at skeletal sites.

Conclusions

Skeletal involvement in paediatric LCH most often presents as ill-defined lytic lesions in the skull and other flat bones, although any bone may be affected. Diagnosis requires careful clinicoradiological assessment and histopathological confirmation when available. Most patients in this cohort had single-system, unifocal disease and achieved excellent outcomes with conservative or systemic therapy as appropriate. Multisystem disease remains more challenging, but favourable outcomes can still be achieved with protocol-based treatment. Early recognition, multidisciplinary evaluation, and long-term follow-up are essential due to the risk of relapse and potential late sequelae.